Quantitative Improvements and Insights into CALB‐Catalyzed Resolution of trans‐ and cis‐2‐Phenylcyclopropyl Azolides

Abstract

With trans‐2‐phenylcyclopropyl azolides as the model substrate for hydrolytic or alcoholic resolution in methyl tert‐butyl ether (MTBE) via Novozym 435 as an immobilized Candida antarctica lipase B (CALB), quantitative improvements of the enzyme activity and enantioselectivity were reported. At the best reaction conditions of 35oC, leading to k2RRKmRR−1=5.185 L/h⋅g and Etrans=97.2, for hydrolysis of trans‐2‐phenylcyclopropyl 1,2,4‐azolide (trans‐2‐PCPT), (1R,2R)‐2‐PCPCA of high optical purity was obtained. Insights into CALB performance via kinetic and thermodynamic analysis for trans‐ and cis‐2‐phenylcyclopropyl 1,2,4‐triazolide (cis‐2‐PCPT) were furthermore addressed, showing the prospect of present kinetic resolution process for synthesizing other optically pure 2‐arylcyclopropane‐1‐carboxylic acids.

Novozym 435: the “perfect” lipase immobilized biocatalyst?

“…315 N435 was used in the resolution of trans-2-phenylcyclopropyl azolides via hydrolysis or alcoholysis in methyl, giving trans-2-phenylcyclopropyl 1,2,4-azolide (trans-2-PCPT) of high optical purity. 316 N435 sequential acetylation/hydrolysis has permitted the production of (S)-C5-lipidic dialkynylcarbinols in 97% ee and (R)-C5-lipidic dialkynylcarbinols in 99% ee from racemic mixtures. 317 2-Phenylpropionic acid was esterified by N435 in bio-based solvents (e.g., p-cymene) in a continuous flow reactor, enabling its kinetic resolution.…”